Current Epidemic of Lung Cancer in Women

Lung cancer is now the number one killer of women, claiming the lives of more women each year than breast cancer, colon cancer, and cervical cancer combined. This shifting paradigm in lung cancer follows the smoking trend and tobacco advertisements targeted to women. The death rate from lung cancer in US women rose 600% from 1930 to 1997 due to increases in smoking (A Report of the Surgeon General; 2001). The incidence of lung cancer among women continues to grow by 0.5% per year. Although smoking is the major cause of lung cancer, nonsmoking women are found to be at greater risk for developing lung cancer than non-smoking men.

Molecular and genetic marker studies identify lung cancer as a collection of genetically distinct diseases. The National Comprehensive Cancer Network (NCCN) guidelines, issued by the American Society of Clinical Oncology (ASCO) for clinical management of lung cancer, recommend treating patients with drugs that target the molecular drivers of their specific tumors. Therefore, molecular and mutation analysis of diagnostic tumor tissue, such as epidermal growth factor receptor (EGFR), is critically important in lung cancer management.

Women, in particular, appear to have more frequent mutations in the EGFR as compared with men. The NCCN guidelines include EGFR mutational analysis as a category 1 recommendation in the evaluation of non-small cell lung cancer. Multiple trials focused on patients with known EGFR activating mutations have demonstrated a better response and progression-free survival for patients receiving an EGFR-tyrosine kinase inhibitor (TKIs), such as erlotinib or gefitinib compared with chemotherapy as first-line therapy. These studies have been shown to identify erlotinib sensitivity in the 88% of patients with wild-type EGFR. In addition, a set of a novel, five-gene expression signatures appeared to predict disease control with erlotinib in refractory non-small cell lung cancer irrespective of EGFR mutation. Disease control at 8 weeks was seen in 83% of patients with one gene signature vs 0% in those without it, and 64% vs 10% in a similar analysis of patients with and without the second signature (Cancer Discovery. 2011;1[1]:OF42). Women survive longer than men, regardless of the stage at diagnosis or treatment, but the overall survival with this disease remains abysmal. We have much work to do. The importance of performing molecular tests at this time, in particular EGFR mutation analysis, with more on the horizon (EML4-ALK), cannot be overemphasized.

Dr. Daya Upadhyay,
Steering Committee Member;
Dr. Heather Wakelee;
and
Dr. Diane Stover, FCCP